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Cited by 1,791Renal cell carcinoma treatmentCancer Immunotherapy and BiomarkersBladder and Urothelial Cancer Treatments

Nivolumab plus Cabozantinib versus Sunitinib for Advanced Renal-Cell Carcinoma

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Choueiri, Toni K., Powles, Thomas, Burotto, Mauricio, Escudier, Bernard, Bourlon, Maria T., Zurawski, Bogdan, Oyervides Juárez, Victor M., Hsieh, James J. +23 more·2021·New England Journal of Medicine
DOI 10.1056/nejmoa2026982PMC PMC8436591
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Abstract

BACKGROUND: The efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known. METHODS: In this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point. RESULTS: Overall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib. CONCLUSIONS: Nivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).

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  • Nivolumab plus cabozantinib was approved by the FDA as the initial-line treatment for RCC, based on CheckMate-9ER.

    “Besides pembrolizumab plus axitinib, nivolumab plus cabozantinib (based on CheckMate-9ER) [112] and avelumab plus axitinib (based on JAVELIN Renal 101) [113] were also approved by the FDA as the initial-line treatment for RCC.”

    From Combination strategies with PD-1/PD-L1 blockade: current advances and future directions (2022) · cites this paper as [112]

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Authors
Choueiri, T. K., Powles, T., Burotto, M., Escudier, B., Bourlon, M. T., Zurawski, B., Oyervides Juárez, V. M., Hsieh, J. J., Basso, U., Shah, A. Y., Suárez, C., Hamzaj, A., Goh, J. C., Barrios, C., Richardet, M., Porta, C., Kowalyszyn, R., Feregrino, J. P., Żołnierek, J., Pook, D., Kessler, E. R., Tomita, Y., Mizuno, R., Bedke, J., Zhang, J., Maurer, M. A., Simsek, B., Ejzykowicz, F., Schwab, G. M., Apolo, A. B., & Motzer, R. J.
Affiliations
  • National Health Service (GB)
  • From the Department of Medical Oncology, Lank Center for Genitourinary Oncology, Dana–Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston (T.K.C.); the Department of Genitourinary Oncology, Barts Cancer Institute, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, Royal Free National Health Service Trust, London (T.P.); the Bradford Hill Clinical Research Center, Santiago, Chile (M.B.); the Department of Medical Oncology,...
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
2021-03-04
Volume
384
Issue
9
Pages
829-841
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejmoa2026982
PMC
PMC8436591
OpenAlex
W3134949580
Cited by
1,791
References
36
Citations by year
2026: 224 · 2025: 281 · 2024: 322 · 2023: 353 · 2022: 407 · 2021: 204
FWCI
209.58
Type
journal article
Language
en
Open access
Licence
www.nejmgroup.org/legal/terms-of-use.htm (vor)
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, cc-by-nc-nd)
Funders
  • Bristol-Myers Squibb Company
  • Ipsen Pharma
  • ONO Pharmaceutical Company Ltd.
  • Exelixis Inc.
  • Takeda Pharmaceutical Company Ltd.
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal cell carcinoma treatment
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
Keywords
nivolumab, cabozantinib, sunitinib, advanced renal cell carcinoma, clear cell renal cell carcinoma, immune checkpoint inhibitors, tyrosine kinase inhibitors, combination therapy, progression-free survival, overall survival, objective response, health-related quality of life, adverse events, immunotherapy, targeted therapy, first-line therapy, subgroup analysis, PD-1
MeSH terms
Sunitinib, Nivolumab, Progression-Free Survival, Adult, Aged, Aged, 80 and over, Anilides, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Renal Cell, Female, Humans, Kidney Neoplasms, Male, Middle Aged, Pyridines, Quality of Life, Proportional Hazards Models, Survival Analysis, Receptor Protein-Tyrosine Kinases, Intention to Treat Analysis, B7-H1 Antigen

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